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Δευτέρα 15 Μαρτίου 2021

Analysis of the cytotoxic effects, cellular uptake and cellular distribution of paclitaxel-loaded nanoparticles in glioblastoma cells in vitro

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Exp Ther Med. 2021 Apr;21(4):292. doi: 10.3892/etm.2021.9723. Epub 2021 Jan 27.

ABSTRACT

Glioblastoma is the most common and aggressive type of brain tumor. Although treatments for glioblastoma have been improved recently, patients still suffer from local recurrence in addition to poor prognosis. Previous studies have indicated that the efficacy of chemotherapeutic or bioactive agents is severely compromised by the blood-brain barrier and the inherent drug resistance of glioblastoma. The present study developed a delivery system to improve the efficiency of delivering therapeutic agents into glioblastoma cells. The anticancer drug paclitaxel (PTX) was packed into nanoparticles that were composed of amphiphilic poly (γ-glutamic-acid-maleimide-co-L-lactide)-1,2-dipalmitoylsn-glycero-3-phosphoethanolaminecopolymer conjugated with targeting moiety transferrin (Tf). The Tf nanoparticles (Tf-NPs) may enter glioblastoma cells via transferrin receptor-mediated endocytosis. MTT assay and flow cytometry were used to explore the cytotoxic effects, cellular uptake and cellular distribution of paclitaxel-loaded nanoparticles. The results indicated that both PTX and PTX-Tf-NPs inhibited the viability of rat glioblastoma C6 cells in a dose-dependent manner, but the PTX-Tf-NPs exhibited a greater inhibitory effect compared with PTX, even at higher concentrations (0.4, 2 and 10 µg/ml). However, both PTX and PTX-Tf-NPs exhibited a reduced inhibitory effect on the viability of mouse hippocampal neuronal HT22 cells compared with that on C6 cells. Additionally, in contrast to PTX alone, PTX-Tf-NPs treatment of C6 cells at lower concentrations (0.0032, 0.0160 and 0.0800 µg/ml) induced increased G2/M arrest, although this difference did not occur at a higher drug concentration (0.4 µg/ml). It was observed that FITC-labeled PTX-Tf-NPs were endocytosed by C6 cells within 4 h. Furthermore, FITC-labeled PTX-Tf-NPs or Tf-NPs co-localized with a lysosomal tracker, Lysotracker Red DND-99. These results of the present study indicated that Tf-NPs enhanced the cytotoxicity of PTX in glioblastoma C6 cells, suggesting that PTX-Tf-NPs should be further explored in animal models of glioblastoma.

PMID:33717235 | PMC:PMC7885080 | DOI:10.3892/etm.2021.9723

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